Recent advances on biocompatible and biodegradable nanoparticles as gene carriers

Introduction: Gene therapy mainly depends on the use of appropriate delivery vehicles with no induction of immune responses and toxicity. The limitations of viral gene carriers such as induction of immunogenicity, random integration in the genome of the host, limitations in the size, has led to a movement toward non-viral systems with much safer properties. Biodegradable and biocompatible polymeric nanocarriers due to several unique properties such as excellent biocompatibility, prolonged gene circulation time, prevented gene degradation, passive targeting by using the enhanced permeability and retention (EPR) effect, and possibility of modulating polymers structure to obtain desirable therapeutic efficacy, are among the most promising systems for gene delivery. However, biodegradable gene delivery systems have some limitations such as inadequate stability and slow release of therapeutics which have to be overcome. Thus, a variety of advanced functional biodegradable delivery systems with more efficient gene delivery activity has recently been introduced. Areas covered: This review summarizes different aspects of biodegradable and biocompatible nano carriers including formulation, mechanism of intracellular uptake, various potential applications of biodegradable nanoparticles and finally recent studies on the therapeutic efficacy of these nanoparticles in sustained delivery of genes

Immune Cell Membrane-Coated Biomimetic Nanoparticles for Targeted Cancer Therapy

Nanotechnology has provided great opportunities for managing neoplastic conditions at various levels, from preventive and diagnostic to therapeutic fields. However, when it comes to clinical application, nanoparticles (NPs) have some limitations in terms of biological stability, poor targeting, and rapid clearance from the body. Therefore, biomimetic approaches, utilizing immune cell membranes, are proposed to solve these issues. For example, macrophage or neutrophil cell membrane coated NPs are developed with the ability to interact with tumor tissue to suppress cancer progression and metastasis. The functionality of these particles largely depends on the surface proteins of the immune cells and their preserved function during membrane extraction and coating process on the NPs. Proteins on the outer surface of immune cells can render a wide range of activities to the NPs, including prolonged blood circulation, remarkable competency in recognizing antigens for enhanced targeting, better cellular interactions, gradual drug release, and reduced toxicity in vivo. In this review, nano-based systems coated with immune cells-derived membranous layers, their detailed production process, and the applicability of these biomimetic systems in cancer treatment are discussed. In addition, future perspectives and challenges for their clinical translation are also presented.Peer reviewe

Recent Advances in Early Diagnosis of Viruses Associated with Gastroenteritis by Biosensors

Gastroenteritis, as one of the main worldwide health challenges, especially in children, leads to 3–6 million deaths annually and causes nearly 20% of the total deaths of children aged < 5 years, of which ~1.5 million gastroenteritis deaths occur in developing nations. Viruses are the main causative agent (~70%) of gastroenteritis episodes and their specific and early diagnosis via laboratory assays is very helpful for having successful antiviral therapy and reduction in infection burden. Regarding this importance, the present literature is the first review of updated improvements in the employing of different types of biosensors such as electrochemical, optical, and piezoelectric for sensitive, simple, cheap, rapid, and specific diagnosis of human gastroenteritis viruses. The Introduction section is a general discussion about the importance of viral gastroenteritis, types of viruses that cause gastroenteritis, and reasons for the combination of conventional diagnostic tests with biosensors for fast detection of viruses associated with gastroenteritis. Following the current laboratory detection tests for human gastroenteritis viruses and their limitations (with subsections: Electron Microscope (EM), Cell Culture, Immunoassay, and Molecular Techniques), structural features and significant aspects of various biosensing methods are discussed in the Biosensor section. In the next sections, basic information on viruses causing gastroenteritis and recent developments for fabrication and testing of different biosensors for each virus detection are covered, and the prospect of future developments in designing different biosensing platforms for gastroenteritis virus detection is discussed in the Conclusion and Future Directions section as well

Poly-dopamine-Beta-Cyclodextrin Modifi ed Glassy Carbon Electrode as a Sensor for the Voltammetric Detection of L-Tryptophan at Physiological pH

ABSTRACT The main purpose of this report was to develop application of poly-dopamine-beta-cyclodextrin modifi ed glassy carbon electrode (PDA-β-CD-GCE) towards electrooxidation and determination of L-Tryptophan (L-Trp) and also the evaluation its kinetic parameters. In continuation of our efforts to use PDA-β-CD-GCE for amino acids detection, our objective in the present work was to expand application of this sensor for the determination of L-Trp which is very sensitive

Synthesis, Characterization and Antioxidant Property of Quercetin-Tb(III) Complex

Purpose: Nearly all of flavonoids are good metal chelators and can chelate many metal ions to form different complexes. This article describes a synthesis of Quercetin–Tb(III) in methanol, characterized by using elemental analysis, UV–visible and evaluation of its antioxidant properties. Methods: The formation of complexes is realized from the UV–visible spectra which shows that the successive formation of Quercetin–Tb(III) occurs. To find out the antioxidant activity variation and the role of Tb(III) ion on the antioxidant activity of the complexes different radical scavenging methods such as: 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and 2,2′-azinobis 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) were used. Results: The results from DPPH, ABTS and FRAP methods showed that Quercetin and Quercetin–Tb(III) complex are capable of donating electron or hydrogen atom, and consequently could react with free radicals or terminate chain reactions in a time- and dose-dependent manner. Conclusion: This study showed that the chelation of metal ions by Quercetin decrease the redox potential of Quercetin-metal complex

Novel insights into the treatment of SARS-CoV-2 infection : An overview of current clinical trials

The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead

Immune checkpoints (ICs) have pivotal roles in regulating immune responses. The inhibitory ICs in the tumor microenvironment (TME) have been implicated in the immune evasion of tumoral cells. Therefore, identifying and targeting these inhibitory ICs might be critical for eliminating tumoral cells. V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel inhibitory IC that is expressed on myeloid cells, lymphoid cells, and tumoral cells; therefore, VISTA can substantially regulate innate and adaptive anti-tumoral immune responses. Besides, growing evidence indicates that VISTA blockade can enhance the sensitivity of tumoral cells to conventional IC-based immunotherapy, e.g., cytotoxic T lymphocyte antigen 4 (CTLA-4) inhibitors. In this regard, the current study aimed to review the current evidence about the structure and expression pattern of VISTA, its role in TME, the clinicopathological significance of VISTA, and its prognostic values in various cancers. Besides, this review intended to collect the lessons from the recent pre-clinical and clinical studies and propose a strategy to overcome tumor immune-resistance states

A scoping review on the potentiality of PD-L1-inhibiting microRNAs in treating colorectal cancer: Toward single-cell sequencing-guided biocompatible-based delivery

Tumoral programmed cell death ligand 1 (PD-L1) has been implicated in the immune evasion and development of colorectal cancer. Although monoclonal immune checkpoint inhibitors can exclusively improve the prognosis of patients with microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) colorectal cancer, specific tumor-suppressive microRNAs (miRs) can regulate multiple oncogenic pathways and inhibit the de novo expression of oncoproteins, like PD-L1, both in microsatellite stable (MSS) and MSI-H colorectal cancer cells. This scoping review aimed to discuss the currently available evidence regarding the therapeutic potentiality of PD-L1-inhibiting miRs for colorectal cancer. For this purpose, the Web of Science, Scopus, and PubMed databases were systematically searched to obtain peer-reviewed studies published before 17 March 2021. We have found that miR-191-5p, miR-382-3p, miR-148a-3p, miR-93-5p, miR-200a-3p, miR-200c-3p, miR-138-5p, miR-140-3p, and miR-15b-5p can inhibit tumoral PD-L1 in colorectal cancer cells. Besides inhibiting PD-L1, miR-140-3p, miR-382-3p, miR-148a-3p, miR-93-5p, miR-200a-3p, miR-200c-3p, miR-138-5p, and miR-15b-5p can substantially reduce tumor migration, inhibit tumor development, stimulate anti-tumoral immune responses, decrease tumor viability, and enhance the chemosensitivity of colorectal cancer cells regardless of the microsatellite state. Concerning the specific, effective, and safe delivery of these miRs, the single-cell sequencing-guided biocompatible-based delivery of these miRs can increase the specificity of miR delivery, decrease the toxicity of traditional nanoparticles, transform the immunosuppressive tumor microenvironment into the proinflammatory one, suppress tumor development, decrease tumor migration, and enhance the chemosensitivity of tumoral cells regardless of the microsatellite state

Molecular beacon strategies for sensing purpose

The improvement of nucleic acid probes as vital molecular engineering devices will cause a noteworthy contribution to developments in bioimaging, biosensing, and disorders diagnosis. The molecular beacon (MB) which was designed by Tyagi and Kramer in 1996, are loop-stem hairpin-designed oligonucleotides armed with a quencher and a dye (also named reporter groups) at the 30 or 50 ends. This construction allows that MBs in the absence of their target complementary molecules do not fluoresce. Through hybridization with their specific targets a spontaneous configuration change on MBs occur and the dye and quencher separate from each other, resulting in emitting the fluorescence. MBs are effective probes for biosensing because of their extraordinary target-specificity, unique structure, inherent fluorescent signal transduction mechanism, low background fluorescence emission, recognition without separation, and favorable thermodynamic properties. In comparison to other probes (such as linear DNA sequences), MBs with the same number of complementary nucleotides matching their target, are multitasking probes. They have advantages of thermodynamic and photostability, flexible ability for conjugation, higher efficient intrinsic signal switching, and ultra-sensitivity. MBs not only are useful for identifying a nucleic acid target but can also be employed for recognition of various non-nucleic acid goals, including heavy metals and cations, enzymes, cells, ATP, etc. Hence, this review highlights the potential of MBs in the improvement of biosensors and their usage in detection of different analytes such as miRNA, mRNA, cocaine, methamphetamine, actin, thrombin, heavy metal and cations and so on. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

A Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

The programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, their effect is mainly focused on improving anti-tumoral immune responses without substantially regulating oncogenic signaling pathways in tumoral cells. Moreover, the conventional immune checkpoint inhibitors cannot impede the de novo expression of oncoproteins, like PD-L1, in tumoral cells. Accumulating evidence has indicated that the restoration of specific microRNAs (miRs) can downregulate tumoral PD-L1 and inhibit TNBC development. Since miRs can target multiple mRNAs, miR-based gene therapy can be an appealing approach to inhibit the de novo expression of oncoproteins, like PD-L1, restore anti-tumoral immune responses, and regulate various intracellular singling pathways in TNBC. Therefore, we conducted the current systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to provide a comprehensive and unbiased synthesis of currently available evidence regarding the effect of PD-L1-inhibiting miRs restoration on TNBC development and tumor microenvironment. For this purpose, we systematically searched the Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web of Science, Ovid, and IranDoc databases to obtain the relevant peer-reviewed studies published before 25 May 2021. Based on the current evidence, the restoration of miR-424-5p, miR-138-5p, miR-570-3p, miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p, and miR-497-5p can inhibit tumoral PD-L1 expression, transform immunosuppressive tumor microenvironment into the pro-inflammatory tumor microenvironment, inhibit tumor proliferation, suppress tumor migration, enhance chemosensitivity of tumoral cells, stimulate tumor apoptosis, arrest cell cycle, repress the clonogenicity of tumoral cells, and regulate various oncogenic signaling pathways in TNBC cells. Concerning the biocompatibility of biomimetic carriers and the valuable insights provided by the single-cell sequencing technologies, single-cell sequencing-guided biomimetic delivery of these PD-L1-inhibiting miRs can decrease the toxicity of traditional approaches, increase the specificity of miR-delivery, enhance the efficacy of miR delivery, and provide the affected patients with personalized cancer therapy